REGULATION OF RECEPTORS ON T-LYMPHOCYTES

在细胞分化过程中发生的变化通常涉及 特定基因的激活和抑制。B和T的共同起源 淋巴细胞提示转录中有重叠的可能性。 调控他们的基因，特别是那些在不久之后表达的基因 这两种血统的分化。这一观点得到了观察结果的支持 免疫球蛋白重链基因在某些T细胞中是活跃的 而后来激活的kappa轻链基因则不是。 因此，早期B细胞和T细胞转录调控的比较 基因(以及控制它们的因素)可能会提供对 启动淋巴细胞的信号。 T细胞受体(TCR)β链基因与白细胞介素2受体 α链基因(IL-2Rpha)在T细胞病变早期均有表达 细胞个体发育。这项提案中概述的实验试图确定 顺式作用序列元件(通过转染试验和分析 转基因小鼠)和相应的反式作用因子 TCR基因在发育上的正确激活。这将允许 未来对这些因素本身的调节研究，可能会在 对环境提示的反应。 IL-2Rα在T细胞活化和最近的报道中进一步被诱导 这表明TRC基因可能也是如此。IL-2Rpha基因 诱导依赖于与诱导物结合的序列基序 核因子-kB。奇怪的是，在TCR基因座上也有一个类似的基序 这表明这两个基因可能受同一因素的调控。 转移到B和T细胞系有望不仅阐明 这个位点的功能作用，但也揭示了其他调节电路 阻止这些基因在B细胞中的结构性表达，其中NR-KB 在宪法上是存在的。

Changes that take place during cell differentiation often involve the activation and repression of specific genes. The common origin of B and T lymphocytes suggests the possibility of overlap in the transcriptional regulation of their genes, particularly those expressed soon after divergence of the two lineages. This idea is supported by the observation that the immunoglobulin mu heavy chain gene is active in some T cells whereas the later activated kappa light chain gene is not. Thus, comparison of the transcriptional regulation of early B and T cell genes (and the factors that control them) may to provide insights into the signals initiating lymphocyte. The T cell receptor (TCR) beta chain gene and the interleukin-2 receptor alpha chain gene (IL-2Ralpha) are both expressed early in the course of T cell ontogeny. Experiments outlined in this proposal seek to identify the cis-acting sequence elements (by transfection assays and analysis of transgenic mice) and the corresponding trans-acting factors that specify the developmentally correct activation of the TCR genes. This will allow future studies on the regulation of the factors themselves, presumably in response to environmental cues. IL-2Ralpha is further inducible upon T cell activation and recent reports suggest that this might be true of the TRC genes as well. IL-2Ralpha gene induction is dependent upon a sequence motif that binds the inducible factor NF-KB. Curiously, a similar motif is located in the TCR locus as well, suggesting that both genes may be regulated by the same factor. Transfections into B and T cell lines is expected to not only clarify the functional role of this site but to also reveal other regulatory circuits that prevent constitutive expression of these genes in B cells where NR-KB is constituitively present.